1-150551891-CAAAAAAA-CAAAA

Variant names:

• chr1-150551891-CAAA-C
• rs199813152
• NM_019032.6:c.-84-301_-84-299delAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_019032.6(ADAMTSL4):​c.-84-301_-84-299delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 118,542 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000032 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0048 (0 hom.)
• Consequence: ADAMTSL4 NM_019032.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.855
• Publications: 0 publications found

Genes affected

ADAMTSL4 (HGNC:19706): (ADAMTS like 4) This gene is a member of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-like gene family and encodes a protein with seven thrombospondin type 1 repeats. The thrombospondin type 1 repeat domain is found in many proteins with diverse biological functions including cellular adhesion, angiogenesis, and patterning of the developing nervous system. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Sep 2014]

ADAMTSL4-AS2 (HGNC:40895): (ADAMTSL4 antisense RNA 2)

MIR4257 (HGNC:38312): (microRNA 4257) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019032.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	NM_019032.6	MANE Select	c.-84-301_-84-299delAAA		intron	N/A	NP_061905.2
	ADAMTSL4	NM_001288608.2		c.-84-301_-84-299delAAA		intron	N/A	NP_001275537.1	Q6UY14-3
	ADAMTSL4	NM_001378596.1		c.-84-301_-84-299delAAA		intron	N/A	NP_001365525.1	Q6UY14-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL4	ENST00000271643.9	TSL:5 MANE Select	c.-84-323_-84-321delAAA		intron	N/A	ENSP00000271643.4	Q6UY14-1
	ADAMTSL4	ENST00000483335.1	TSL:1	n.1802_1804delAAA		non_coding_transcript_exon	Exon 3 of 3
	ADAMTSL4	ENST00000369039.9	TSL:5	c.-84-323_-84-321delAAA		intron	N/A	ENSP00000358035.5	Q6UY14-3

Frequencies

GnomAD3 genomes AF: 0.0000324 AC: 3 AN: 92708 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000116

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000210

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000236

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00238 AC: 9 AN: 3788 AF XY: 0.00297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00667

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad NFE exome AF: 0.00226

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00480 AC: 124 AN: 25834 Hom.: 0 AF XY: 0.00580 AC XY: 77 AN XY: 13284

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00649 AC: 5 AN: 770

American (AMR) AF: 0.00555 AC: 7 AN: 1262

Ashkenazi Jewish (ASJ) AF: 0.00107 AC: 1 AN: 932

East Asian (EAS) AF: 0.00394 AC: 6 AN: 1524

South Asian (SAS) AF: 0.00490 AC: 5 AN: 1020

European-Finnish (FIN) AF: 0.00388 AC: 5 AN: 1290

Middle Eastern (MID) AF: 0.00210 AC: 1 AN: 476

European-Non Finnish (NFE) AF: 0.00527 AC: 89 AN: 16892

Other (OTH) AF: 0.00300 AC: 5 AN: 1668

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000324 AC: 3 AN: 92708 Hom.: 0 Cov.: 30 AF XY: 0.0000458 AC XY: 2 AN XY: 43706

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26418

American (AMR) AF: 0.000116 AC: 1 AN: 8594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2326

East Asian (EAS) AF: 0.00 AC: 0 AN: 3298

South Asian (SAS) AF: 0.00 AC: 0 AN: 3056

European-Finnish (FIN) AF: 0.000210 AC: 1 AN: 4752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 180

European-Non Finnish (NFE) AF: 0.0000236 AC: 1 AN: 42374

Other (OTH) AF: 0.00 AC: 0 AN: 1188

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs199813152; hg19: chr1-150524367;